Synapse formation, synapse stabilization and neurotrophic effects on ionic channels were studied using neurons and muscle cells in culture. Synapses were detected and investigated by electrophysiological recording. Single ionic conductances were studied with the extracellular patch clamp technique on cultured muscle cells or on bilayers formed at the tip of patch pipets. Neurons from chick spinal cord form stable synapses with muscle cells in culture, eliciting changes in the muscle cell membrane that resemble maturation in vivo. Stabilization of synapses leads to increased aggregation of muscle acetylcholine receptors, blocking of a Ca2+-dependent K+-conductance and increased tetrodotoxin sensitivity of the action potential mechanism. Blocking of the Ca2+-dependent K+-conductance can be elicited in the absence of innervation after treatment of muscle cells with a low molecular weight fraction (Less than 4,000 D) obtained from chick spinal cord conditioned medium or with a spinal cord extract. Calcium channel blockers impair the ability of dissociated neurons to form synapses, and inhibit neurite extension. The degree of inhibition depends on the age in ovo and is more marked in neurons dissociated from older embryos. Synapse formation is also impaired by purified monoclonal antibodies directed against the acetylcholine receptor in muscle cells. A mechanism by which a change in electrical activity at a synapse results in a local structural change was proposed; and was used to show competition between neighboring afferent inputs leads to selective synaptic stabilization, and to suggest a role for dendritic spines in reducing this competition.